KATPchannels process nucleotide signals in muscle thermogenic response

Santiago Reyes, Sungjo Park, Andre Terzic, Alexey E. Alekseev

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations

Abstract

Uniquely gated by intracellular adenine nucleotides, sarcolemmal ATP-sensitive K+ (KATP) channels have been typically assigned to protective cellular responses under severe energy insults. More recently, KATP channels have been instituted in the continuous control of muscle energy expenditure under non-stressed, physiological states. These advances raised the question of how KATP channels can process trends in cellular energetics within a milieu where each metabolic system is set to buffer nucleotide pools. Unveiling the mechanistic basis of the KATP channel-driven thermogenic response in muscles thus invites the concepts of intracellular compartmentalization of energy and proteins, along with nucleotide signaling over diffusion barriers. Furthermore, it requires gaining insight into the properties of reversibility of intrinsic ATPase activity associated with KATP channel complexes. Notwithstanding the operational paradigm, the homeostatic role of sarcolemmal KATP channels can be now broadened to a wider range of environmental cues affecting metabolic well-being. In this way, under conditions of energy deficit such as ischemic insult or adrenergic stress, the operation of KATP channel complexes would result in protective energy saving, safeguarding muscle performance and integrity. Under energy surplus, downregulation of KATPchannel function may find potential implications in conditions of energy imbalance linked to obesity, cold intolerance and associated metabolic disorders.

Original languageEnglish (US)
Pages (from-to)506-519
Number of pages14
JournalCritical Reviews in Biochemistry and Molecular Biology
Volume45
Issue number6
DOIs
StatePublished - Dec 2010

Keywords

  • ATPase
  • Kir6.2
  • SUR
  • diffusion
  • energy expenditure
  • metabolism
  • phosphotransfer
  • structure modeling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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